Vaccination with Flt3L-induced CD8¦Á⁺ dendritic cells prevents CD4⁺ T helper cell-mediated experimental autoimmune myocarditis

详细信息    查看全文

• 作者：Alan Valaperti ; Mototsugu Nishii ; Davide Germano ; Peter P. Liu ; Urs Eriksson
• 关键词：EAM ; experimental autoimmune myocarditis ; Th ; CD4+ T helper ; Flt3L ; FMS-like tyrosine kinase 3 ligand ; MyHC ; myosin heavy-chain
• 刊名：Vaccine
• 出版年：2013
• 出版时间：1 October, 2013
• 年：2013
• 卷：31
• 期：42
• 页码：4802-4811
• 全文大小：3787 K

文摘

Experimental autoimmune myocarditis (EAM) represents a CD4⁺ T helper (Th) cell-mediated mouse model of inflammatory heart disease. Interferon (IFN)-¦Ã, typically produced by Th1 cells, reduces EAM severity in myosin heavy-chain-(MyHC)-¦Á peptide/Complete Freund adjuvant-immunized mice. Thus, developing a vaccination strategy that promotes differentiation of Th1 cells may be beneficial in EAM.

FMS-like tyrosine kinase 3 ligand (Flt3L)-induced splenic CD8¦Á⁺ dendritic cells (DC), which produce interleukin (IL)-12p35, were identified to selectively induce biased differentiation towards Th1. Mice vaccinated with MyHC-¦Á-loaded Flt3L-induced splenic CD8¦Á⁺ DC were protected from EAM. In contrast, when Flt3L-induced splenic CD8¦Á⁺ DC were pre-stimulated and over-activated with LPS and ¦ÁCD40 antibodies or loaded with unspecific OVA^323-339 peptide instead of MyHC-¦Á peptide, mice developed similar disease scores as non-vaccinated controls. Vaccination efficacy depended on IFN-¦Ã, since CD8¦Á⁺-vaccinated IFN-¦ÃR^?/? mice were not protected. Importantly, splenic CD8¦Á⁺ vaccination was independent of regulatory T cells.

Taken together, Flt3L-induced dendritic cell-based antigen-specific vaccination limits expansion of auto-reactive Th cells and protects mice from autoimmune heart inflammation.